{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T08:13:28Z","timestamp":1792052008614,"version":"4.4.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":245,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013465","name":"Association Fran\u00e7aise contre les Myopathies (AFM)-T\u00e9l\u00e9thon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013465","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Agence Nationale de la Recherche\u2014Jeunes Chercheuses et Jeunes Chercheurs","award":["ANR-22-CE13-0043"],"award-info":[{"award-number":["ANR-22-CE13-0043"]}]},{"name":"LABEX CORTEX","award":["ANR-11-LABX-0042"],"award-info":[{"award-number":["ANR-11-LABX-0042"]}]},{"name":"Universite\u0301 de Lyon"},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["417982926"],"award-info":[{"award-number":["417982926"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["535112684"],"award-info":[{"award-number":["535112684"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DFG Emmy-Noether Grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Nicotinic acetylcholine receptors are widely expressed in the peripheral and central nervous systems. Mutations in acetylcholine receptor-subunit genes have been associated with neuromuscular diseases, such as arthrogryposis multiplex congenita (AMC) and epilepsy. We report a patient with arthrogryposis, severe muscle weakness and neurodevelopmental delay. During his first year of life, he developed therapy-refractory epilepsy. Using whole-exome sequencing, we identified the compound pathogenic variants c. 875G&amp;gt;A (p. Cys292Tyr) and c. 959delA (p. Gln320Argfs*25) in the cysteine-rich with epidermal growth factor-like domain protein 1 gene (CRELD1, NM_001077415.3). Recently, functional studies have shown that CRELD1 is a membrane-associated endoplasmic reticulum-resident protein disulphide isomerase that acts as a maturation enhancer of AChR biogenesis, thereby controlling the abundance of functional receptors at the cell surface. To test pathogenicity, we took advantage of the genetics and extremely rapid genome editing in Caenorhabditis elegans. We were able to model these heterozygous variants and observed a decrease in AChRs at the neuromuscular junction. Hence, our study identifies compound heterozygous CRELD1 variants responsible for a rare neurodevelopmental disorder characterized by arthrogryposis, muscle weakness and epilepsy.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf326","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T19:11:25Z","timestamp":1756926685000},"source":"Crossref","is-referenced-by-count":2,"title":["Biallelic <i>CRELD1<\/i> variants cause severe muscle weakness and infantile epilepsy"],"prefix":"10.1093","volume":"7","author":[{"given":"Manuela","family":"D'Alessandro","sequence":"first","affiliation":[{"name":"Univ Lyon, University Claude Bernard Lyon 1, MeLiS, CNRS UMR 5284, INSERM U 1314 , Lyon 69008 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Bamborschke","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne 50931 ,","place":["Germany"]},{"name":"Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne 50937 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6006-8507","authenticated-orcid":false,"given":"Margret H","family":"B\u00fclow","sequence":"additional","affiliation":[{"name":"Life and Medical Sciences Institute, University of Bonn , Bonn 53115 ,","place":["Germany"]},{"name":"Klinik f\u00fcr Herzchirurgie, Cure3D lab, Department Membrane Contact Sites, Universit\u00e4tsklinikum D\u00fcsseldorf , D\u00fcsseldorf 40225 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zkan","family":"\u00d6zdemir","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne 50931 ,","place":["Germany"]},{"name":"Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne 50937 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00fclya-Sevcan","family":"Daimag\u00fcler","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne 50931 ,","place":["Germany"]},{"name":"Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne 50937 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Br\u00fcmmer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne 50937 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of Cologne , Cologne 50937 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Deckert","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne 50937 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Wunderlich","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne 50937 ,","place":["Germany"]},{"name":"Center for Rare Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne 50937 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Koerber","sequence":"additional","affiliation":[{"name":"Department of Pediatric Radiology, Faculty of Medicine and University Hospital Cologne, 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